Valencia Hernández, Carlos Andrés; (2021) Arterial stiffness, cardiovascular risk and physical functioning in the Whitehall II study. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

BACKGROUND: Arterial stiffness measured by carotid-femoral Pulse Wave Velocity (cf-PWV) is a predictor of cardiovascular events, incident hypertension and a cross-sectional marker of low physical functioning. This thesis aims to expand the knowledge on the bidirectional relationship between cf-PWV and incident hypertension, investigate the predictive value of a second cf-PWV measurement and study its prospective effects on physical function. METHODS: Data from 5236 participants of the Whitehall II study from 2008 to 2019 were used to examine the relationship between incident hypertension and baseline arterial stiffness, as well as arterial stiffness progression among different blood pressure status subgroups. Linear mixed models were used to assess the progression in cf-PWV between subgroups and logistic regression models were used to estimate the odds of incident hypertension. The risk of clinical events was validated through hospital health records and analysed using survival models with a mean follow-up of 11.2 years. The prospective relationship between arterial stiffness and change in standardised measures of physical functioning 8 years later was assessed using linear mixed models. RESULTS: A bidirectional relationship between arterial stiffness and hypertension was observed. Participants in the highest tertile of cf-PWV at baseline had three times higher odds of incident hypertension than participants in the first tertile. Participants with uncontrolled blood pressure at baseline had the highest increase in cf-PWV compared to normotensives. Change between two measurements of a-PWV did not improve the C-statistic but adding a single measurement to the 10-year atherosclerotic cardiovascular disease score improved both the C-statistic and the net reclassification index. Baseline and prospective change of cf-PWV were associated to decline in the scores of the physical component of the SF-36 questionnaire and the instrumental activities of daily living. CONCLUSIONS: The bidirectional relationship between arterial stiffness and hypertension shown in some studies was replicated in the Whitehall II cohort. The sample size allowed for subgroup comparisons that were previously unpowered in previous studies. A second compared to a single measurement of cf-PWV did not seem to improve the predictive ability of cardiovascular risk models. Higher C-statistic and net reclassification index for prediction models using the components of the 10-year atherosclerotic cardiovascular disease score were seen after including cf-PWV. Finally, cf-PWV is a prospective marker of decrease in standardised measures of physical functioning.

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